USPTO Patents Application 09993647

United States Patent and Trademark Office

UNITED STATES DEPARTMENT OF COMMERCE
United States Patent and Trademark Office

Address: COMMISSIONER FOR PATENTS
P.O. Box 1450

Alexandria, Virginia 22313-1450
www.uspto.gov

APPLICATION NO.

FILING DATE

FIRST NAMED INVENTOR

ATTORNEY DOCKET NO.

CONFIRMATION NO.

09/993,647 11/27/2001 Bernd Riedl BAYER 18A 1010

23599 7590 04/25/2008

MILLEN, WHITE, ZELANO & BRANIGAN, P.C.
2200 CLARENDON BLVD.
SUITE 1400

ARLINGTON, VA 22201

EXAMINER

RAO, DEEPAK R

PAPER NUMBER

1624

MAIL DATE

04/25/2008

DELIVERY MODE

PAPER

Please find below and/or attached an Office communication concerning this application or proceeding.

The time period for reply, if any, is set in the attached communication.

PTOL-90A (Rev. 04/07)

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Application No.

09/993,647

Applicant(s)

RIEDL ET AL.

Examiner

Deepak Rao

Art Unit

1624

- The MAILING DATE of this communication appears on the cover sheet with the correspondence address —
Period for Reply

A SHORTENED STATUTORY PERIOD FOR REPLY IS SET TO EXPIRE 3 MONTH(S) OR THIRTY (30) DAYS,
WHICHEVER IS LONGER, FROM THE MAILING DATE OF THIS COMMUNICATION.

- Extensions of time may be available under the provisions of 37 CFR 1 .136(a). In no event, however, may a reply be timely filed
after SIX (6) MONTHS from the mailing date of this communication.

- If NO period for reply is specified above, the maximum statutory period will apply and will expire SIX (6) MONTHS from the mailing date of this communication.

- Failure to reply within the set or extended period for reply will, by statute, cause the application to become ABANDONED (35 U.S.C. § 133).
Any reply received by the Office later than three months after the mailing date of this communication, even if timely filed, may reduce any
earned patent term adjustment. See 37 CFR 1 .704(b).

Status

1 )^| Responsive to communication(s) filed on 26 December 2007 .
2a )£3 This action is FINAL. 2b)^ This action is non-final.

3) \Z\ Since this application is in condition for allowance except for formal matters, prosecution as to the merits is

closed in accordance with the practice under Ex parte Quayle, 1935 CD. 11, 453 O.G. 213.

Disposition of Claims

4) |EI Claim(s) 74,81,87,93,99-104,106-115 and 117-119 is/are pending in the application.

4a) Of the above claim(s) is/are withdrawn from consideration.

5) D Claim(s) is/are allowed.

6) |EI Claim(s) 74.81.87.93.99-104.106-115 and 117-119 is/are rejected.

7) D Claim(s) is/are objected to.

8) \Z\ Claim(s) are subject to restriction and/or election requirement.

Application Papers

9) L~H The specification is objected to by the Examiner.

10)D The drawing(s) filed on is/are: a)^ accepted or b)^ objected to by the Examiner.

Applicant may not request that any objection to the drawing(s) be held in abeyance. See 37 CFR 1.85(a).
Replacement drawing sheet(s) including the correction is required if the drawing(s) is objected to. See 37 CFR 1.121(d).
The oath or declaration is objected to by the Examiner. Note the attached Office Action or form PTO-152.

Priority under 35 U.S.C. § 119

12)fJ Acknowledgment is made of a claim for foreign priority under 35 U.S.C. § 1 19(a)-(d) or (f).
a)Q All b)Q Some * c)Q None of:

1 0 Certified copies of the priority documents have been received.

20 Certified copies of the priority documents have been received in Application No. .

30 Copies of the certified copies of the priority documents have been received in this National Stage
application from the International Bureau (PCT Rule 17.2(a)).
* See the attached detailed Office action for a list of the certified copies not received.

Attach ment(s)

1 ) □ Notice of References Cited (PTO-892)

2) Q Notice of Draftsperson's Patent Drawing Review (PTO-948)

3) O Information Disclosure Statement(s) (PTO/SB/08)

Paper No(s)/Mail Date .

4) l~l Interview Summary (PTO-41 3)

Paper No(s)/Mail Date. .

5) Q Notice of Informal Patent Application

6) □ Other: .

U.S. Patent and Trademark Office

PTOL-326 (Rev. 08-06)

Office Action Summary

Part of Paper No./Mail Date 20080423

Application/Control Number: 09/993,647 Page 2

Art Unit: 1624

DETAILED ACTION

Claims 74, 81, 87, 93, 99-104, 106-115 and 117-119 are pending in this application.

The following rejections are maintained:

1. Claims 74, 81, 87, 93, 99-103, 106-114 and 117 are rejected under 35 U.S.C. 112, first
paragraph, because the specification, while being enabling for a method for the treatment of
carcinoma of the colon (based on the in vitro treatment of the tumor cell lines HCT1 16 and
DLD-1 provided in the specification), does not reasonably provide enablement for a method for
the treatment of all types of solid tumors, carcinomas, myeloid disorders or adenomas; or a
method for inhibiting RAF-kinase in a human or mammal. The specification does not enable any
person skilled in the art to which it pertains, or with which it is most nearly connected, to use the
invention commensurate in scope with these claims. The reasons provided in the previous office
action(s) are incorporated here by reference.

Applicant's arguments have been fully considered but they were not found to be
persuasive. Applicant relies on the state of the art references, Kolch and Monia and argues that
'the references teach correlation of raf inhibition with the inhibition of the growth of a variety of
tumor types'. Contrary to applicant's arguments, the state of the art references Kolch and/or
Monia do not establish a therapeutic method for the treatment of all types of solid tumors,
carcinomas, myeloid disorders or adenomas generally. As explained in the previous office
action, the state of the art is not indicative of the fact that treatments of all types of diseases
encompassed by the instant claims are conventional or well known. The cited references are too
speculative and invite further research into treatment of cancer diseases. For example, Monia at

Application/Control Number: 09/993,647 Page 3

Art Unit: 1624

page 668 provides that "the emergence of novel therapies that specifically reverse the oncogenic
effect of these gene products has generally been slow". All references provided as evidence of
enabling disclosure present no evidence that the claimed compounds actually have activity in
treating all types of solid tumor, carcinoma, myeloid disorders or adenoma. There is no evidence
of record that the claimed compounds are actually efficacious in treating all types of solid tumor,
carcinoma, myeloid disorders or adenoma; or inhibit RAF-kinase generally.

Applicant's arguments based on the state of the art references - Monia, Kolch, Daum,
WO 98/22103, etc. have been fully considered but not deemed to be persuasive. However, the
cited references do not cure the deficiencies of the specification. Considered separately or
together, these references invite further research into the treatment of solid tumor, carcinoma,
myeloid disorder, adenoma, etc. through inhibition of RAF-kinase.

Applicant argues that 'Given the extent of the disclosure provided, it would at most
involve routine experimentation for one of ordinary skill in the art to treat any of the other
cancers with the named compounds'. The guidance in the specification is limited to an in vitro
cell proliferation assay showing inhibition of two colon cancer cell lines; and summary
instructions relating to an in vivo assay in mice that can be performed to determine the inhibition
of a human adenocarcinoma cell line (see pages 94-96). There is no evidence of record how the
provided data is directly involved in the pathogenesis of all types of solid tumors, carcinoma,
myeloid disorders or adenoma and/or that simply inhibiting RAF-kinase will lead to treatment of
all of these diseases. It is not routine for one skilled in the art to synthesize, purify, screen for
RAF-kinase inhibition, and test for anticancer activity of the claimed compounds.

Application/Control Number: 09/993,647 Page 4

Art Unit: 1624

Applicant argues that 'claim 1 17 is drawn to a method of inhibiting raf-kinase in a human
or other mammal and examiner has not identified any element of the claim for which the
disclosure is deficient'. Claim 1 17 is directed towards 'a method for inhibiting RAF -kinase in a
human or mammal' - which involves administering of the compound to human or mammal and
therefore reaches through to the treatment of all types of diseases associated with RAF-kinase.
The findings and conclusions in the cited publications are with respect to inhibition of RAF
kinase and the application of such activity for specific types of cancerous growth. The
development of the most efficacious strategy for the treatment of cancers is based on
understanding the underlying mechanisms of carcinogenesis. This includes the knowledge that
the carcinogenic process is a multi-step, multi-mechanism process and that no two cancers are
alike, in spite of some apparent universal characteristics, such as their inability to have growth
control, to terminally differentiate, to apoptose abnormally and to have an apparent extended or
immortalized life span. Since tumor promotion phase involves multiple mechanisms, there is no
existence of a single therapeutic approach. The evidence of record does not disclose any known
compounds of similar structure, which have been demonstrated to inhibit RAF-kinase generally
and thereby treat all diseases mediated by raf kinase; or treat all types of solid tumors,
carcinomas, myeloid disorders or adenomas, when the compounds are administered to a human
or a mammal.

2. Claims 74, 81, 87, 93, 99-104, 106-1 15 and 117-119 are provisionally rejected under the
judicially created doctrine of obviousness-type double patenting as being unpatentable over

Application/Control Number: 09/993,647 Page 5

Art Unit: 1624

claims 38, 89-91, 121 of copending Application No. 10/042,226. It is acknowledged that
'applicants will address the rejection when the instant claims are otherwise allowable'.

Conclusion

THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time
policy as set forth in 37 CFR 1.136(a).

A shortened statutory period for reply to this final action is set to expire THREE
MONTHS from the mailing date of this action. In the event a first reply is filed within TWO
MONTHS of the mailing date of this final action and the advisory action is not mailed until after
the end of the THREE-MONTH shortened statutory period, then the shortened statutory period
will expire on the date the advisory action is mailed, and any extension fee pursuant to 37
CFR 1 .136(a) will be calculated from the mailing date of the advisory action. In no event,
however, will the statutory period for reply expire later than SIX MONTHS from the mailing
date of this final action.

Any inquiry concerning this communication or earlier communications from the
examiner should be directed to Deepak Rao whose telephone number is (571) 272-0672. The
examiner can normally be reached on Monday-Friday from 8:00am to 5:00pm.

If attempts to reach the examiner by telephone are unsuccessful, the examiner's
supervisor, James O. Wilson, can be reached at (571) 272-0661 . The fax phone number for the
organization where this application or proceeding is assigned is (571) 273-8300.

Any inquiry of a general nature or relating to the status of this application or proceeding
should be directed to the receptionist whose telephone number is (571) 272-1600.

Application/Control Number: 09/993,647 Page 6

Art Unit: 1624

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may be obtained from either Private PAIR or Public PAIR. Status information for unpublished
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system, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free).

April 24, 2008

/Deepak Rao/
Primary Examiner
Art Unit 1624